The relationship between ras genes, metalloproteinase expression, and metastatic behavior was studied in two metastatic models, i.e., an N-nitrosomethylurea (NMU)-induced mammary carcinoma and 433 cell lines derived from NIH/3T3 cells transfected with v-H-ras, and a glucocorticoid promoter. There was no quantitative relationship between ras DNA levels and the malignant phenotype. Similarly, ras levels of individual metastases varied, some were higher, while others were lower than the parent tumor. Dexamethasone-mediated induction of the p2l ras protein expression resulted in a 2.5-fold decrease in metastatic capacity, as well as the type IV collagenolytic activity of the 433 cells. Type IV collagenolytic activity of the NMU-induced rat mammary carcinomas was higher than that of the normal rat breasts, but metastases did not differ from the primary tumors. Both the NMU-induced tumors and the 433 cell lines expressed two gelatinolytic metalloproteinases of 65 and 92 kDa, whereas only the 65 kDa enzyme was expressed by normal rat breast tissue, a rat fibroma, and NIH/3T3 cells. The data from two tumor models suggest that ras amplification or increased expression is not essential for the development of metastases. This study has been completed and a manuscript submitted for publication.